RNA binding protein as monodisperse carriers for siRNA delivery

Abstract

siRNA is a powerful gene silencing tool that suppresses the expression of the disease-causing protein by degrading its mRNA directly. It exhibits the profound potential in drug development with applications in both target validation and disease intervention. The most established methods for nonviral delivery of siRNA employ the use of nanoparticles, in particular, the cationic nanocarriers. Despite the popularity and feasibility, nanoparticle-based delivery carriers possess some undesired features such as polydisperse sizes, heterogeneous contents, nonspecific binding and technical challenges on large-scale fabrication, which limit their efficacy and potential in clinic utility. Protein-based siRNA carriers show the potentiality to solve some of these problems faced by nanoparticle carriers. In this review, we surveyed the current studies of using RNA binding proteins for siRNA packing and targeted delivery. RNA binding protein recognizes siRNA independent of charges, thus assembles into monodisperse carrier that has a discrete structure and drug ratio. This review discusses the most widely used RNA binding protein, including dsRBD, p19 and U1A RBD. Chemical and genetic modification to modulate the proteins' functionalities is also covered. Keywords: dsRBD, siRNA delivery, Protein carrier, RNA binding protein